Erythromycin A has been used for the treatment of gram positive infections in man for nearly three decades. However, this antibiotic is unreliably absorbed when administered orally, and causes gastrointestinal disturbances such as cramping, nausea, vomiting and diarrhea. It also has a relatively short serum half-life of 2-3 hours in man, and rapidly loses its antibacterial activity in an environment of high acidity (pH 4).
Unreliable absorption of an antibiotic makes control of an infection difficult. Although variation in absorption can be offset by administration of larger doses, higher doses of erythromycin can produce severe gastrointestinal side-effects, as has become apparent from recent clinical studies on intravenous administration of erythromycin lactobionate.
Because of the short serum half-life of erythromycin, administration of three to four doses of antibiotic per day are usually necessary to maintain effective blood levels. It would be desirable to administer the antibiotic only once or twice per day to make patient compliance easier.
Finally, the sensitivity of erythromycin to acid requires carefully designed dosage forms to ensure protection from stomach acidity, yet the antibiotic formulation must efficiently release erythromycin in a less acidic environment, such as the intestine.
It has now been found that certain novel compounds incorporating chemical modifications of both the cladinose sugar and the macrolide ring of erythromycin overcome the above-mentioned problems.